Percutaneous coronary interventions such as angioplasty are a safe, effective way to open blocked coronary arteries. Initially, angioplasties were performed only with a balloon. An important advance of this technique was the development of stents, which are small expandable, usually metallic, tubular structures that are introduced up to the site of the obstruction and used to keep the artery open.
Despite the huge advance made with this technique (more than one million surgeries of this kind are performed per year worldwide), the long-term results are still not satisfactory due to the onset of restenosis. Restenosis is the vessel reocclusion that occurs, generally at 6 months, after an initially successful percutaneous coronary intervention. Unlike atherosclerotic lesions, restenosis is a lesion healing process in response to damage to the artery wall induced during the placement of the stent.
In order to try to overcome the problem of restenosis, development has begun on stents that incorporate drugs, what is known as Drug Eluting Stents (DES). Although the drug can be incorporated into the stent directly in reservoirs constructed in the stent, the DES generally consist of stents coated with polymers into which the drug has been incorporated, either by chemically bonding the drug to the polymer or more usually by embedding the drug inside the polymer.
The polymer to be used in DES must meet a number of extremely stringent requirements. Among others, it must be stable, biocompatible, and neither thrombogenic nor proinflammatory. It also must allow loading with sufficient amounts of the anti-restenosis drug to obtain the desired dosing levels and must be capable of releasing the drug in a controlled manner over a period of various weeks. In particular, however, the polymer must exhibit elevated adhesion to the metal surface of the stent as well as high flexibility and absence of crack-bridging, since it is necessary that the polymer coating of the stent does not fracture, peel off from the surface of the stent or become deformed when the stent is expanded during use, where stent expansion up to the required diameter at the site of the lesion can mean deforming it up to 300%.
Finding a polymer that fulfills all these requirements is currently one of the most important challenges in the field of DES, and it can be stated that the ideal coating for this kind of application has still not been developed.
WO 01/17578 describes a series of polymeric derivatives carrying triflusal or HTB based on homo- or copolymerization of an acrylic-type monomer carrying triflusal or HTB. As examples of polymers, the preparation of a homopolymer resulting from polymerization of 2-(methacryloyloxy)ethyl 2-acetyloxy-4-(trifluoromethyl)benzoate (THEMA) is described, as well as THEMA copolymers with N,N-dimethylacrylamide (DMA) or 2-acrylamido-2-methylpropanesulphonic acid (AMPS). The polymers described in this patent are indicated as useful for the coating of non-biological materials that will come into contact with blood during their use such as vascular prostheses, artificial cardiac valves, and stents due to their good properties from the standpoint of thrombogenicity.
Although the examples of polymers described in WO 01/17578 are stable, biocompatible, and show good anti-thrombogenic properties, they are not suitable for use as coating in DES since they do not have good adhesion to the stent surface nor sufficient flexibility to withstand the mechanical deformation that occurs during the manufacture and use of a stent.
There remains the need, thus, to find new polymers suitable for use as stent coating, and in particular having appropriate physico-mechanical properties including good adhesion to the stent and the capability of being stretched without flaking or cracking.